Efficacy and Safety of Afatinib in the Treatment of Advanced Non-Small-Cell Lung Cancer with EGFR Mutations: A Meta-Analysis of Real-World Evidence

Abstract

Introduction. The purpose of this study was to explore the efficacy and safety of afatinib in advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations based on real-world evidence. Materials and Methods. Eligible real-world studies were identified from PubMed, Cochrane Library, and Embase. Cochrane guidelines were used to assess the quality of included studies. Cochran’s Q test and I2 statistics were used for the heterogeneity analysis. Results. Twenty-five studies were included in this meta-analysis; nine studies were included in the qualitative descriptive analysis. The summarized disease control rate (DCR) was 87.6% (81.5%, 92.7%), and the overall response rate (ORR) was 58.9% (48.8%, 68.7%). The pooled median progression-free survival (PFS) was 12.4 (10.3, 14.5) months, mean time to failure (TTF) was 15.4 (13.6, 17.2) months, and median overall survival (OS) was 31.6 (26.7, 36.5) months. The total incidences of adverse events (AEs) for skin rashes, diarrhea, paronychia, and mucositis were 71.4% (64.4%, 77.9%), 70.4% (60.1%, 79.8%), 52.1% (41.9, 62.3%), and 36.5% (29.5%, 43.8%), respectively. The incidences of severe adverse events (SAEs, Grade ≥3) for diarrhea, skin rashes, paronychia, and mucositis were 9.7% (6.8%, 13.1%), 5.8% (4.5%, 7.2%), 3.8% (2.0%, 6.2%), and 2.1% (1.0%, 3.6%), respectively. Differences in PFS and OS between the afatinib non-full-dose (<40 mg) and full-dose (>40 mg) groups were not significant ( P > 0.05 ). However, the ORR in the full-dose group was 78.5% (66.7%, 88.4%), which was significantly higher than that in the non-full-dose group (67.8% [56.8%, 77.9%]). Conclusion. The efficacy and safety of afatinib has been confirmed by real-world evidence in advanced NSCLC with EGFR mutation, consistent with randomized controlled trial results. In real-world setting, tolerability-guided dose adjustment might not affect the afatinib efficacy.

Does dose reduction of afatinib affect treatment outcomes of patients with EGFR-mutant metastatic non-small cell lung cancer in real-world clinical practice?

“…This is in keeping with afatinib’s effectiveness as first-line treatment in patients with EGFR -mutant advanced NSCLC, which has been well established in clinical trials and real-world studies ( 4 , 6 - 9 , 16 , 17 , 21 - 25 ). Afatinib also has a good tolerability profile but as some patients do experience gastrointestinal and cutaneous AEs, tolerability-guided dose reduction has been suggested ( 8 , 9 , 22 , 25 ). In our study, patients on lower doses of afatinib had lower discontinuation rate due to AEs than those on standard dose.…”

The Efficacy and Safety of Afatinib in Non-Small Cell Lung Cancer Patients with Brain Metastasis: A Meta-Analysis

“…Overall, this is also consistent with the conclusion of the LUX-Lung3/6 trails. It should be noted that we did not stratify the oral dose of afatinib in our selected studies because a meta-analysis reported no diference between the efcacy of the 30-mg group and the 40-mg groups [21]. Te common AEs of afatinib include skin rash, diarrhea, loss of appetite, stomatitis, vomiting, fatigue, and paronychia.…”